Surgery Shows Survival Benefit in Early Prostate Ca

Action Points

Explain that further follow-up of a Scandinavian study showed that patients undergoing radical prostatectomy had a survival advantage over those treated with watchful waiting.

Note that the advantage was seen only in patients under the age of 65, but that subgroup analyses were hampered by lack of power.

Y﻿ounger men with early-stage prostate cancer had a significantly lower mortality risk with radical prostatectomy compared with watchful waiting, long-term follow-up from a Scandinavian study showed.

Surgery was associated with almost a 50% reduction in the relative risk of prostate cancer death at 15 years among men younger than 65 with low-risk disease, as reported in the May 5 issue of the New England Journal of Medicine. All-cause mortality was about 40% lower.

The results in younger men with low-risk prostate cancer drove the overall outcome, which showed a 38% reduction in prostate cancer mortality with radical prostatectomy, Anna Bill-Axelson, MD, PhD, of University Hospital in Uppsala, Sweden, and co-authors wrote.

Men ages 65 and older did not benefit significantly from radical prostatectomy versus watchful waiting, regardless of disease characteristics.

"The benefit is obvious among men younger than 65 years of age, but it is still unclear whether the benefit extends to older men," the investigators wrote.

The number needed to treat (NNT) declined from 19 in an earlier analysis to 15 after a median follow-up of 12.8 years. Among men younger than 65, the NNT was seven.

The findings came from the latest analysis of the Scandinavian Prostate Cancer Group Study Number 4. Earlier analyses showed a significant reduction in prostate cancer mortality and death from any cause in men randomized to radical prostatectomy versus watchful waiting. However, the benefit was limited to men younger than 65.

In the earlier analyses, too few prostate cancer deaths had occurred among men with low-risk disease to determine whether that subgroup also benefited from surgery, the authors noted. Longer follow-up offered the potential to make that determination.

The trial involved 695 men with early-stage prostate cancer, randomized from October 1989 to February 1999 to surgery or watchful waiting. The study population had a mean age of 65 and a baseline PSA level that averaged 13 ng/mL.

By the end of 2009, 166 men in the surgery group and 201 in the watchful-waiting arm had died. The estimated 15-year mortality was 46% with surgery and 52.7% with watchful waiting, which translated into a 25% reduction in the relative risk of death in favor of prostatectomy (P=0.007).

The authors found that 55 men in the radical-prostatectomy arm and 81 in the watchful-waiting group had died of prostate cancer, a 38% reduction in the relative risk (P=0.01). The incidence of distant metastasis was 4.8% in the prostatectomy arm and 18.6% with watchful waiting, a 41% reduction in relative risk (P<0.001).

Subgroup analysis showed that surgically treated men younger than 65 had significant reductions in relative risk for overall mortality, prostate cancer mortality, and distant metastases, averaging about 50%. In contrast, surgery did not significantly reduce the risk of any of the three endpoints in older men.

The study population included 263 men with low-risk prostate cancer, defined as a PSA level <10 ng/mL and either a Gleason score <7 or WHO grade 1. In that subgroup, surgery was associated with significant reduction in all-cause mortality (31.4% versus 44.6%, P=0.02) and the risk of distant metastases (9.9% versus 21.4%, P=0.008) but not prostate cancer mortality (6.8% versus 11.0%, P=0.14).

Further stratified by age, the data showed that men younger than 65 with low-risk prostate cancer also derived significant benefits from surgery with respect to all-cause mortality and distant metastases, but surgery did not improve mortality or the risk of distant metastases in older men.

"The accruing numbers of events for the older age group indicate that in our study, a reduction in disease-specific mortality is unlikely ever to become apparent in this age group, owing to competing causes of death," the authors wrote in conclusion.

Limitations of the study included lack of power in the subgroup analyses, differences in screening and biopsy protocols for low-risk patients treated with active surveillance now versus at the time of enrollment in the study, and reliance on medical record review versus patient report for symptom severity.

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